The ever-changing world of dendritic spines

Santiago Ramón y Cajal originally described spines in the dendrites of neurons in the cerebellum back in the late 19th century, but it wasn’t until the mid 1950’s with the development of the electron microscope that these structures were shown to be synaptic structures. Although it has been known that the number of dendritic spines changes during development and in association with learning, most studies have inferred the changes by looking at static time points rather than monitoring individual spines in the same animal over time, partly, due to the difficulty of tracking a single structure of about 0.1 micrometer in size (0.0001 mm). But new advances in imaging technology have allowed researchers to ‘follow’ individual spines over time both in vitro and in the whole animal.

Purkinje Cell by S Ramon y Cajal

Dendritic spines are no longer thought of as the static structures of Ramón y Cajal’s (or even my) generation, but rather dynamic structures that can be added and eliminated from individual dendrites. And because each spine is associated with a synaptic input, and because their structure and dynamic turnover is known to have a profound effect on neuronal signaling, one cannot but be tempted to propose that they are associated with specific aspects of memory formation.

Two developments have made it possible to monitor individual dendritic spines at different time points in the same animal: the ability to incorporate fluorescent molecules into transgenic mice that make the spines visible under fluorescent illumination, and the development of in vivo transcranial two photon imaging that allow researchers to go back to that individual dendrite and monitor how the dendritic spines change over time. Two papers published in Nature make use of these techniques to look at how dendritic spines change in the motor cortex of mice that have learned a motor task.

In one, Guang Yang, Feng Pan and Wen-Biao Gan looked at how spines changed when either young or adult mice were trained in to learn specific motor strategies. They observed that spines underwent significant turnover, but that learning the motor task increased the overall number of new spines and that a small proportion of them could persist for long periods of time. They calculated that although most of the newly formed spines only remained for about a day and a half, a smaller fractions of them could still persist for either a couple of months or a few years. Based on their data they suggest that about 0.04% of the newly formed spines could contribute to lifelong memory.

Dendritic spine by Tmhoogland

Another study by Tonghui Xu, Xinzhu Yu, Andrew J. Perlik, Willie F. Tobin, Jonathan A. Zweig, Kelly Tennant, Theresa Jones and Yi Zuo did a similar experiment, but using a different motor training task. Like the Yang group, they also saw that training leads to both the formation and elimination of spines. Although newly formed spines are initially unstable, a few of them can become stabilized and persist longer term. Further, training made newly formed spines more stable and preexisting spines less stable. The authors interpret their results as an indication that during learning there is indeed a ‘rewiring’ of the network and not just addition of new synapses.

The two papers were reviewed by Noam E. Ziv & Ehud Ahissar in the News and Views section. Here they raise the issue that, if such a small number of spines are to account for the formation of stable memories, then what are the consequences of the loss of a somewhat larger number of spines on the neuronal network?

For someone like me that more than once as an undergraduate used a microscope fitted with a concave mirror to use the sunlight to illuminate the specimen, the ability to monitor individual synaptic structures over time in a living organism can only be described as awesome. But, as pointed out by Ziv and Ahissar,

“[…] although it remains to be shown conclusively that these forms of spine remodeling are essential components of long-term learning and not merely distant echoes of other, yet to be discovered processes, these exciting studies make a convincing case for a structural basis to skill learning and reopen the field for new theories of memory formation.”